A tail-flick assay for anesthesia in Drosophila melanogaster has been improved and refined. We established a protocol that yields reliable measures of anesthetic potency that under conditions when the fruit fly has equilibrated with the anesthetic gas. The assay has been used to refine the genetic map location for two alleles of a gene that affects the response to anesthetics and to provide the first evidence for genetic loci that interact with a second anesthesia gene. The issue of uniformity of anesthetic action has been analyzed by comparing the effects of genetic variations on the effectiveness of different general anesthetics. The results provide evidence for the existence of subgroups of anesthetics that have related action at their target(s) and they place severe limits on the degree to which different anesthetics can have identical action at a single target. The importance of ion channels has been investigated by determining the alteration in general anesthesia caused by mutations in the components of these structures. The results show that ion channels impinge on the anesthetic pathway in non-trivial ways. Comparison of anesthetic effects in two different assays suggests that challenge by anesthetics can delineate the importance of particular ion channels for different behaviors.